Atrial Fibrillation Is Associated with a 5-Fold Increased Risk for Stroke and Is Estimated to Cause 15% of All Strokes (2)

Home , Atrial fibrillation, Auscultation, Fibrillation, Signs and symptoms

Peter Zimetbaum,MD Physician Writer Sankey Williams,MD Darren Taichman, MD Deborah Cotton,MD,MPH Section Editors Fibrillation Atrial In theClinic © 2010 AmericanCollegeofPhysicians judgment. The informationcontainedhereinshouldneverbeusedasasubstituteforclinical fibrillation. CME Objective:To reviewcurrentevidencefor thediagnosisandtreatmentofatrial (Physicians’ InformationandEducationResource) education resourcesofthe The contentof and otherresourcesreferencedineachissueof http://pier.acponline.org, http://www.acponline.org/products_services/mksap/15/?pr31, Readers whoareinterestedintheseprimaryresourcesformoredetailcanconsult ers. Editorialconsultantsfrom and PublishingDivisionwiththeassistanceofsciencewritersphysician writ- Clinic and Self-AssessmentProgram). CME Questions Patient Information Tool Kit Practice Improvement Treatment Diagnosis from theseprimarysourcesincollaborationwiththeACP’s MedicalEducation In theClinic American CollegeofPhysicians is drawnfromtheclinicalinformationand PIER Annals ofInternalMedicine and MKSAP In theClinic provide expertreviewofthecontent. MKSAP (ACP), including . editors develop (Medical Knowledge page ITC6-16 page ITC6-15 page ITC6-14 page ITC6-14 page ITC6-2 page ITC6-6 PIER In the In the Clinic trial fibrillation (AF) is the most common, clinically significant cardiac arrhythmia. It occurs when a diffuse and chaotic pattern of elec- Atrical activity in the atria suppresses or replaces the normal sinus mechanism, leading to deterioration of mechanical function. Atrial fibrillation is a major cause of morbidity, mortality, and health care expenditures; prevalence in the United States is 2.3 million cases and is estimated to increase to 5.6 million by the year 2050 (1). Atrial fibrillation is associated with a 5-fold increased risk for stroke and is estimated to cause 15% of all strokes (2). Independent of coexisting diseases, the presence of AF confers a 2-fold increased risk for all-cause mortality (3). Diagnosis Who is at risk for atrial Is a single electrocardiogram fibrillation? sufficient to diagnose or exclude Atrial fibrillation occurs in less atrial fibrillation? than 1% of individuals aged 60 to Figure 1 is an electrocardiogram 65 years, but in 8% to 10% of those (ECG) showing AF, and it indi- older than 80 years. Prevalence is cates that a single ECG is sufficient higher in men than in women and to diagnose AF provided it is higher in whites than in blacks (1). recorded during the arrhythmia. The risk for AF increases with the However, AF is often paroxysmal, presence and severity of underlying so a single ECG showing normal heart failure and valvular disease. rhythm does not exclude the diagnosis. Monitoring for a longer time What symptoms and signs should can be helpful when AF is suspect- cause clinicians to suspect atrial ed and the initial ECG is normal. fibrillation? In patients with daily symptoms, Some patients have prominent 24- or 48-hour continuous Holter symptoms, including palpitations, monitoring is usually sufficient to shortness of breath, exercise intol- make the diagnosis. In patients with erance, chest pain, and malaise. less-frequent symptoms, monitoring However, many patients, particular- during longer periods with electro- ly the elderly, have asymptomatic cardiographic loop recorders may be (silent) AF, including some patients necessary. However, even monitor- who have severe symptoms during ing for periods as long as a month other AF episodes (4). Symptoms can be nondiagnostic in patients are generally greatest at disease on- with very infrequent episodes. In set—when episodes are typically addition, because patients must turn paroxysmal—and tend to diminish loop recorders on after symptoms over time, especially when the begin, these recorders are not help- arrhythmia becomes persistent. ful in detecting asymptomatic ar- Symptoms result from elevation rhythmias or arrhythmia-associated of ventricular rate (either at rest or nonspecific symptoms that the pa- exaggerated by exercise), irregular tient may not recognize as being re- 1. Kannel WB, Benjamin ventricular rate, and loss of atrial lated to AF. It may take years to EJ. Current percep- tions of the epidemi- contribution to cardiac output. confirm the diagnosis of AF in ology of atrial fibrillation. Cardiol Clin. some patients because they have 2009; 27: 13-24. On physical examination, signs of nonspecific symptoms and long pe- [PMID: 19111760] AF include a faster-than-expected 2. Hart RG, Benavente O, riods between episodes. McBride R, Pearce LA. heart rate, which varies greatly Antithrombotic therapy to prevent stroke from patient to patient, an “irregu- Some newer devices avoid these in patients with atrial larly irregular” time between heart problems. New types of event mon- fibrillation: a meta- analysis. Ann Intern sounds on auscultation, and periph- itors detect irregular ventricular Med. 1999;131:492- eral pulses that vary irregularly in rhythms and automatically start 501. [PMID: 10507957] both rate and amplitude. recording regardless of symptoms.

In addition, implanted pacemakers which may someday have therapeu- and implantable defibrillator– tic implications. cardioverters with atrial leads identify and record both symptomatic What other electrocardiographic and asymptomatic AF. Other new arrhythmias can be confused with devices continuously record heart atrial fibrillation? rhythms for as long as a month and Other arrhythmias that are com- wirelessly transmit data to a central monly confused with AF include si- monitoring station, where automat- nus rhythm with frequent premature ed systems interpret cardiac atrial contractions, atrial flutter, and rhythms and report diagnoses in atrial tachycardia. The key electro- real time (4a). cardiographic findings of AF are the absence of P waves and the presence What is the role of history and of an irregular ventricular rhythm physical examination in patients without a recurring pattern. When with atrial fibrillation? an irregular rhythm is present but History and physical examination the diagnosis of AF is uncertain, cli- help determine the duration of nicians should examine long record- symptoms and identify potential ings from multiple leads looking for underlying causes. Clinicians partially obscured P waves in de- 3. Benjamin EJ, Wolf PA, D’Agostino RB, et al. should seek historical and physical formed T waves and ST segments. Impact of atrial fibril- evidence of hypertension, heart lation on the risk of death: the Framing- failure, cardiac surgery, murmurs Figure 2 is an ECG of an irregular ham Heart Study. Cir- indicative of stenotic or regurgitant rhythm that might be attributed to culation. 1998;98:946- 52. [PMID: 9737513] valvular disease, and other indica- AF, but the presence of P waves 4. Page RL, Wilkinson and other features identify sinus WE, Clair WK, et al. tions of structural heart disease. In Asymptomatic ar- addition, clinicians should look for rhythm with frequent premature rhythmias in patients with symptomatic signs and symptoms of noncardiac atrial contractions. Figure 3 is an paroxysmal atrial fib- causes of AF, including pulmonary ECG of another irregular rhythm rillation and paroxysmal supraventricular disease, hyperthyroidism, use of that might be attributed to AF, but tachycardia. Circula- tion. 1994;89:224-7. adrenergic drugs (such as those the presence of “saw-tooth” P waves [PMID: 8281651] used to treat pulmonary disease) or and a ventricular response that 4a. Zimetbaum P, Gold- man A. Ambulatory other stimulants, and use of alco- varies from 2:1 atrioventricular arrhythmia monitor- hol. A family history might identify conduction to 4:1 atrioventricular ing: choosing the right device. Circula- first-degree relatives with AF, conduction identifies atrial flutter. tion. 2010;122:1629-36

5. American College of Cardiology/American Heart Association Figure 3. Atrial flutter. Classic “saw-tooth” flutter waves are seen in all 12 leads, and the ventricular Task Force on Prac- tice Guidelines. response is mostly regular. (There is a transient change from 2:1 to 4:1 atrioventricular conduction fol- ACC/AHA/ESC 2006 Guidelines for the lowing the 12th QRS complex.) Management of Pa- tients with Atrial Fib- rillation: a report of the American College How should clinicians classify “Permanent” AF means that the ar- of Cardiology/Ameri- can Heart Association atrial fibrillation? rhythmia is continuous, and interven- Task Force on Prac- Although knowledgeable observers tions to restore sinus rhythm have ei- tice Guidelines and the European Society disagree on the answer to this ques- ther failed or not been attempted. of Cardiology Com- tion, the most accepted convention mittee for Practice The same patient may be classified Guidelines (Writing categorizes AF as paroxysmal, persist- into different categories at different Committee to Revise the 2001 Guidelines ent, or permanent (5) (Box 1). times, so clinicians should classify pa- for the Management “Paroxysmal” AF means that episodes of Patients With Atrial tients according to the current pattern Fibrillation): devel- terminate without intervention in or most common pattern. oped in collaboration with the European fewer than 7 days (often within 24 Heart Rhythm Associ- hours). “Persistent” AF means that These distinctions are useful ation and the Heart Rhythm Society. Cir- episodes last longer than 7 days or re- because they predict responses culation. quire an intervention, such as car- to therapy. For example, patients 2006;114:e257-354. [PMID: 16908781] dioversion, to restore sinus rhythm. are less likely to respond to

© 2010 American College of Physicians ITC6-4 In the Clinic Annals of Internal Medicine 7 December 2010 antiarrhythmic drug therapy as the but also coronary artery disease, Classification of Atrial Fibrillation pattern goes from paroxysmal to valvular heart disease, or cardiomy- Paroxysmal: Episodes spontaneously persistent to permanent. Patients in opathy. Atrial fibrosis occurs fre- terminate within 7 days all 3 categories, however, require quently with structural heart dis- Persistent: Episodes last >7 days and anticoagulation. ease, and many people consider require intervention to restore sinus atrial fibrosis central to the ar- rhythm What laboratory studies should rhythmia’s pathogenesis. “Lone” AF Permanent: Interventions to restore sinus clinicians obtain in patients newly refers to AF in the absence of heart rhythm have either failed or have not been attempted diagnosed with atrial fibrillation? disease. Some experts believe that When patients initially present with the diagnosis of lone AF should be AF, clinicians should measure serum restricted to patients younger than electrolytes and thyroid-stimulating 60 years of age because it is diffi- hormone to identify possible causes. cult to exclude structural heart They should measure blood tests for disease in older patients (6). renal and hepatic function to guide the selection of drug therapy and Some acute illnesses are associated check a stool Hemoccult test before with AF, including acute myocardial starting anticoagulation. Transtho- infarction, pulmonary embolism, and racic echocardiography helps deter- thyrotoxicosis. Atrial fibrillation oc- mine the patient’s potential respon- curs in approximately 40% of pa- siveness to antiarrhythmic therapy by tients after cardiac or thoracic sur- measuring left atrial size and assess- gery, but it may also occur after other ing for valvular heart disease, peri- types of major surgery or during a cardial disease, and left ventricular severe illness. Obesity and sleep ap- 6. Furberg CD, Psaty BM, hypertrophy. A transesophageal nea are associated with an increased Manolio TA, et al. echocardiogram to exclude atrial clot incidence of AF. Prevalence of atrial fibrillation in elderly is indicated when transthoracic im- subjects (the Cardio- ages are inadequate or cardioversion Atrial fibrillation also occurs in vascular Health Study). Am J Cardiol. is planned in a patient who has been people who have no predisposing 1994;74:236-41. conditions. These patients are typi- [PMID: 8037127] therapeutically anticoagulated for 7. Naito M, David D, less than 3 weeks. In patients with cally men 40 to 50 years of age, and Michelson EL, et al. symptoms often occur at night, at The hemodynamic appropriate clinical indications, addi- consequences of car- tional tests may be appropriate to rest, following vigorous exercise, or diac arrhythmias: evaluation of the rel- evaluate the patient for pulmonary with alcohol use. The mechanisms ative roles of abnor- are unclear but may involve in- mal atrioventricular embolism, acute myocardial infarc- sequencing, irregular- tion, or acute heart failure. creases in circulating catechola- ity of ventricular mines, changes in myocardial rhythm and atrial fibrillation in a canine What underlying conditions conduction times and refractory model. Am Heart J. 1983;106:284-91. should clinicians look for in periods, and increases in vagal tone. [PMID: 6869209] patients with atrial fibrillation? Other forms of AF without known 8. Risk factors for stroke and efficacy of an- Eighty percent of patients with AF underlying conditions occur during tithrombotic therapy have structural heart disease, partic- waking hours and are preceded by in atrial fibrillation. Analysis of pooled ularly hypertensive heart disease emotional stress or exercise. data from five randomized controlled trials. Arch Intern Med. 1994;154:1449- Diagnosis... Atrial fibrillation is the most common clinically significant cardiac 57. [PMID: 8018000] 9. Brand FN, Abbott RD, arrhythmia, and its prevalence increases with advancing age. Typical symptoms Kannel WB, Wolf PA. include palpitations, shortness of breath, and exercise intolerance. However, some Characteristics and prognosis of lone patients report only general malaise, and many patients are asymptomatic. Elec- atrial fibrillation. 30- trocardiogram recordings during episodes are the only way to confirm the diag- year follow-up of the nosis. If the diagnosis is suspected and the ECG is normal, longer monitoring with Framingham Study. JAMA. 1985:254:3449- a loop recorder or a Holter monitor can be helpful. The initial assessment should 53. [PMID: 4068186] include laboratory tests for electrolytes, thyroid-stimulating hormone, and renal 10. Hart RG, Sherman DG, Easton JD, and hepatic function to rule out underlying disorders or contraindications to Cairns JA. Prevention therapies. An echocardiogram should be done to look for structural heart disease. of stroke in patients with nonvalvular atrial fibrillation. Neurology. CLINICAL BOTTOM LINE 1998;51:674-81. [PMID: 9748009]

7 December 2010 Annals of Internal Medicine In the Clinic ITC6-5 © 2010 American College of Physicians Treatment What are the complications of infarction, hypotension, or high Situations in Which Patients atrial fibrillation, and how can risk for acute stroke. Patients with with Atrial Fibrillation May therapy decrease the risk for AF and the Wolff-Parkinson- Require Hospitalization these events? White syndrome can have ex- • Uncertain or unstable underly- There are 3 reasons to treat AF: to tremely rapid atrioventricular con- ing arrhythmia reduce symptoms, to prevent duction mediated by the accessory • Acute myocardial infarction, al- thromboembolism, and to prevent pathway, which can be a poten- tered mental status, decompen- cardiomyopathy. sated heart failure, or hypotension tially life-threatening condition • Intolerable symptoms despite and require urgent cardioversion. hemodynamic stability Although AF is not always symp- • Elective cardioversion (if moni- tomatic, the symptoms can be dis- Which patients with atrial tored outpatient setting is not abling. Symptoms are usually fibrillation should clinicians available) caused by inappropriately rapid consider hospitalizing? • Acute anticoagulation if very- ventricular rates or the irregularity Although AF is usually managed in high risk for stroke of the ventricular response (7). The an outpatient setting, clinicians • Telemetry monitoring during initiation of certain drugs loss of atrial contribution to ven- should consider hospitalizing pa- • Procedures such as cardiac tricular filling (“atrial kick”) is well tients with AF when management catheterization, electrophysio- tolerated by most patients except requires close monitoring for safety logic studies, pacemakers, im- those with ventricular hypertrophy (12) (Box 2). plantable defibrillators, or from long-standing hypertension, catheter or surgical ablation aortic stenosis, and hypertrophic Should clinicians attempt rate obstructive cardiomyopathy. control or rhythm control? Traditionally, most clinicians have 11. Redfield MM, Kay Stroke is the most common form preferred rhythm control to rate GN, Jenkins LS, et al. Tachycardia-related of arterial thromboembolism dur- control, but recent, high-quality cardiomyopathy: a ing AF. In patients with nonvalvu- common cause of clinical trials have shown that ventricular dysfunc- lar AF, the average annual risk for rhythm control generally does not tion in patients with atrial fibrillation re- arterial thromboembolism, includ- improve mortality, stroke, hospital- ferred for atrioven- ing stroke, is 5%, and the risk is ization, or quality of life compared tricular ablation. Mayo Clin Proc. higher in patients older than age 75 with rate control (13, 14). Rate 2000;75:790-5. [PMID: 10943231] years (8). The risk is related to spe- control is easier to accomplish and 12. Chung MK. Schweik- cific features of AF as well as other prevents exposure to the potential ert RA. Wilkoff BL, et al. Is hospital admis- risk factors for thromboembolism adverse effects of antiarrhythmic sion for initiation of (9). Left atrial thrombi cause 75% antiarrhythmic ther- agents. On the other hand, rhythm apy with sotalol for of strokes in patients with AF (10). control may be useful in selected atrial arrhythmias required? Yield of in- patients with severe symptoms (be- hospital monitoring It is important to treat the tachycardia fore or after failure of rate control) and prediction of of AF because it can lead to risk for significant ar- or in younger patients without rhythmia complica- cardiomyopathy if left untreated (11). tions. JACC. structural heart disease. 1998;32:169-76. [PMID: 9669266] When should clinicians consider The AFFIRM (Atrial Fibrillation Follow-up 13. Atrial Fibrillation Fol- low-up Investigation immediate cardioversion in Investigation of Rhythm Management) tri- of Rhythm Manage- patients with atrial fibrillation? al included 4060 patients with AF who had ment (AFFIRM) In- vestigators. A com- Prompt cardioversion should be at least 1 risk factor for stroke. The mean parison of rate age was 69 years, and structural heart dis- control and rhythm considered for new-onset AF control in patients when the duration of the arrhyth- ease, aside from hypertension, was unusu- with atrial fibrillation. al. All-cause mortality at 5 years was 25.9% N Engl J Med. mia is less than 48 hours. One ex- 2002;347:1825-33. ample is a hospitalized patient on in the rate-control group and 26.7% in the [PMID: 12466506] rhythm-control group (P = 0.080). Patients 14. Hohnloser SH, Kuck cardiac monitoring. Most patients KH, Lilienthal J. with apparently successful rhythm control Rhythm or rate con- with AF do not require immediate still needed anticoagulation because of trol in atrial fibrilla- cardioversion, but it can obviate tion—Pharmacolog- persistent stroke risk, and patients who ical Intervention in the need for anticoagulation and were able to maintain sinus rhythm had a Atrial Fibrillation (PIAF): a randomised may be appropriate in selected pa- survival advantage that was almost bal- trial. Lancet. tients with decompensated heart anced by the disadvantage imposed by 2000;356:1789-94. [PMID: 11117910] failure, severe angina or acute antiarrhythmic drug therapy (15).

© 2010 American College of Physicians ITC6-6 In the Clinic Annals of Internal Medicine 7 December 2010 A more recent trial extended these obser- What strategies should clinicians vations to patients with severe heart fail- consider for rhythm control in ure by randomly assigning 1376 patients patients with atrial fibrillation? with AF, left ventricular ejection fraction Rhythm control is no longer the of ≤35%, and heart failure symptoms to preferred strategy in most patients rate control versus rhythm control. At 37 months, death from cardiovascular dis- with AF. The trials comparing ease occurred in 25% of the rate-control rate control with rhythm control, group and in 27% of the rhythm-control however, have not included group (P = 0.6). There was no improve- younger patients or those with 15. AFFIRM Investiga- ment in all-cause mortality, stroke, heart highly symptomatic AF. There- tors. Relationships between sinus failure, or need for hospitalization in the fore, it is reasonable to consider rhythm, treatment, rhythm-control group (16). and survival in the rhythm control in these patients. Atrial Fibrillation Fol- Also, experienced clinicians often low-Up Investigation What strategies should clinicians of Rhythm Manage- prefer rhythm control for the first ment (AFFIRM) consider for rate control in episode of symptomatic AF in Study. Circulation. patients with rapid atrial 2004;109:1509-13. younger patients because many [PMID: 15007003] fibrillation? 16. Atrial Fibrillation and maintain sinus rhythm without Congestive Heart Clinicians should consider drug Failure Investigators. antiarrhythmic drug treatment af- Rhythm control ver- therapy to control ventricular rate in ter cardioversion. sus rate control for all patients with AF, even if rhythm atrial fibrillation and heart failure. N Engl control is eventually done. Although Patients can be converted to nor- J Med. 2008;358:2667-77. criteria for rate control vary with pa- mal sinus rhythm with direct elec- [PMID: 18565859] tient age, the traditional target has trical current or with drugs. Elec- 17. American College of Cardiology/Ameri- been heart rates of 60 to 80 beats per trical cardioversion is indicated can Heart Associa- tion Task Force on minute at rest and between 90 to when the patient is hemodynami- Practice Guidelines. 115 beats per minute during moder- cally unstable. When the patient is ACC/AHA/ESC 2006 Guidelines for the ate exercise (17). However, a recent hemodynamically stable, the con- Management of Pa- study comparing a strategy of lenient version rate with antiarrhythmic tients with Atrial Fib- ≤ rillation. Circulation. rate-control (resting heart rate 110 drugs is lower than that with elec- 2006;114:e257-354. [PMID: 16908781] beats per minute) with a strategy of trical direct current but does not 18. Van Gelder IC, strict rate control (≤ 80 beats per Groenveld HF, Crijns require deep sedation or general HJGM, et al. Lenient minute), found no advantage to the anesthesia and may facilitate the versus Strict rate control in patients stricter rate control strategy (18). choice of antiarrhythmic drug ther- with atrial fibrillation. Recommended first-line therapy to N Engl J Med. apy to prevent recurrence. 2009;12;360:668-78. decrease atrioventricular nodal con- [PMID: 20231232] β Patients should receive therapy to 19. Davy JM, Herold M, duction includes -blockers and Hoglund C, et al. nondihydropyridine calcium-channel achieve both rate control and ade- Dronedarone for the control of ventricular antagonists (Table 1). A recently ap- quate anticoagulation before elective rate in permanent proved antiarrhythmic medication, direct current or pharmacologic car- atrial fibrillation: the Efficacy and safety of dronedarone, has also been shown to dioversion of AF more than 48 dRonedArone for the cOntrol of ven- be safe and modestly effective for hours in duration. In addition, the tricular rate during rate control of AF (19). serum potassium level should be atrial fibrillation (ER- ATO) study. Am greater than 4.0 mmol/L, serum Heart J. Digitalis and amiodarone block the 2008;156:527.e1-9. magnesium level should be greater [PMID:18760136] atrioventricular node but are not rec- than 1.0 mmol/L, and ionized calci- 20. Vassallo P. Trohman RG. Prescribing ommended as first-line monotherapy um levels should be greater than 0.5 amiodarone: an evi- for rate control (17). Digitalis does dence-based review mmol/L. In most cases, cardiover- of clinical indica- not reduce the tachycardia that oc- sion should be performed in a moni- tions. JAMA. curs with exercise, and it is unlikely 2007;298:1312-22. tored hospital setting to permit ade- [PMID: 17878423] to control rate in patients with heart 21. Maisel WH, Kuntz quate assessment of the degree of KM, Reimold SC, et failure and high sympathetic activity. rate control, bradycardia, proarrhyth- al. Risk of initiating Amiodarone is occasionally used to antiarrhythmic drug mic affects of antiarrhythmic agents, therapy for atrial fib- reduce ventricular response if other and other adverse effects (21). rillation in patients admitted to a uni- agents have failed, but this practice is versity hospital. Ann difficult to justify because of the as- Antiarrhythmic drugs other than Intern Med. 1997;127:281-4. sociated toxicities (20). amiodarone generally have equal [PMID: 9265427]

7 December 2010 Annals of Internal Medicine In the Clinic ITC6-7 © 2010 American College of Physicians Table 1. Drug Therapy for Rate and Rhythm Control in Atrial Fibrillation Agent Mechanism of Action Dosage Benefits Side Effects Notes Rate-Controlling Agents ß-Blockers

Metoprolol Selective ß1-adrenergic– 5 mg IV every 5 min, Convenient IV Bradycardia, hypotension, receptor blocking agent up to 15 mg 50–100 administration in NPO heart block, mg PO twice daily patients, rapid onset of bronchospasm (less action, dependable AV frequently than nonselective nodal blockade ß-blockers), worsening of CHF Propranolol Nonselective ß-adrenergic– 1–8 mg IV (1 mg every Inexpensive, commonly Bradycardia, hypotension, receptor blocking agent 2 min). 10–120 mg PO available heart block, bronchospasm, 3 times daily; long- worsening of CHF acting preparation: 80–320 mg PO once daily.

Esmolol Short-acting IV ß1 0.05–0.2 mg/kg per Short-acting, titratable Bradycardia, hypotension, Occasionally selective adrenergic min IV on or off with very rapid heart block, bronchospasm inconsistent effect in receptor-blocking agent half-life (less frequent) high-catecholamine states Pindolol Nonselective ß-adrenergic– 2.5–20 mg PO 2–3 Less bradycardia, less Bradycardia, hypotension, Less propensity for receptor blocking agent times daily bronchospasm heart block heart block than with intrinsic sympatho- other ß-blockers mimetic activity

Atenolol Selective ß1-adrenergic– 5 mg IV over 5 min, Does not cross blood– Bradycardia, hypotension, receptor blocking agent repeat in 10 min. brain barrier, fewer heart block 25–100 mg PO once CNS side effects daily Nadolol Nonselective ß-adrenergic– 20–120 mg once daily Lower incidence of Bradycardia, hypotension, Oral form only receptor blocking agent crossing blood–brain heart block barrier, fewer CNS side effects Calcium-channel blockers Verapamil Calcium-channel blocking 5–20 mg in 5-mg Consistent AV nodal Hypotension, heart block, Do not use in the agent increments IV every blockade direct myocardial depression Wolff–Parkinson– 30 min, or 0.005 mg/kg White syndrome per min infusion. 120–360 mg PO daily, in divided doses or in the slow-release form. Diltiazem Calcium-channel blocking 0.25–0.35 mg/kg IV Consistent AV nodal Hypotension, heart block, less Do not use in the agent followed by 5–15 mg/h. blockade myocardial depression Wolff–Parkinson– 120–360 mg PO daily White syndrome as slow release Cardiac glycoside Digoxin Na+/K+ pump inhibitor, 0.75–1.5 mg PO or IV Particularly useful for Heart block, digoxin- First-line therapy increases intracellular in 3–4 divided doses rate control in CHF associated arrhythmias; only in patients with calcium over 12–24 h. dosage adjustment required decreased left- Maintenance dose: in renal impairment ventricular systolic 0.125 mg PO or IV to function. Not useful 0.5 mg daily for rate control with exercise. Not useful for conversion of AF or aflutter to NSR. Antiarrhythmic agents Class Ia Procainamide Prolongs conduction 1–2 g q 12 h (shorter- Convenient IV dosing Not recommended because Need to follow drug and slows repolarization acting oral preparations available with of frequent side effects, levels and QT interval by blocking inward Na+ are no longer available) maintenance infusion, including hypotension, for toxicity, adjust flux and conversion to PO nausea, vomiting, dose in patients with tablets, very effective lupus-like syndrome, QT renal insufficiency. at converting AF to prolongation, and Not for use in patients NSR arrhythmia with severe LV dysfunction. Quinidine Prolongs conduction and gluconate slows repolarization. 324–648 mg PO Relatively effective in Proarrhythmia, nausea, Not recommended Blocks fast inward Na+ every 8–12 h converting AF to NSR vomiting, diarrhea, because of frequent channel but may take several QT prolongation side effects. Follow days to achieve NSR drug levels and QT inter- because of PO dosing val for toxicity. Adjust dose in patients with renal insufficiency. Oral agent only.

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© 2010 American College of Physicians ITC6-8 In the Clinic Annals of Internal Medicine 7 December 2010 Table 1 (continued). Drug Therapy for Rate and Rhythm Control in Atrial Fibrillation Agent Mechanism of Action Dosage Benefits Side Effects Notes Antiarrhythmic agents Class Ia Disopyramide Similar electrophysiologic 150 mg PO every Can be useful in QT prolongation (not PR Rarely used in current era properties to procainamide 6–8 h, or 150–300 mg patients with or QRS), torsades de of antiarrhythmic therapy. and quinidine twice a day hypertension and pointes, heart block Oral agent only, negative normal LV function inotropic properties. Class Ic Flecainide Blocks Na+ channels 2 mg/kg, IV. 50–150 Efficacy in paroxysmal Aflutter or atrial tachycardia Not for use in (and fast Na+ current) mg PO every 12 h. AF with structurally with rapid ventricular patients with Also, single loading normal hearts response but not with acute structurally abnormal doses of 300 mg are single loading doses. VT hearts efficacious in conversion and VF in diseased hearts of recent onset AF. Propafenone Blocks myocardial 2 mg/kg, IV. 150–300 Efficacy in paroxysmal Aflutter or atrial tachycardia Antiarrhythmic and Na+ channels mg PO every 8 h. Also, and sustained AF with rapid ventricular response, weak calcium channel single loading doses of but not with acute single and ß-blocking 600 mg are efficacious loading doses properties. Not for in conversion of recent use with structural onset AF. heart disease. Class III Ibutilide Prolongs action potential 1 mg IV over 10 min. Efficacy in acute and Polymorphic VT (torsades de In some centers, only used duration (and atrial and May be repeated once rapid conversion of AF pointes) occurred in 8.3% in the electrophysiology ventricular refractoriness) if necessary. to NSR of patients in a clinical trial laboratory. May also be by blocking rapid (most with LV dysfunction), used to facilitate component of delayed QT prolongation unsuccessful direct- rectifier potassium current current rectifier potassium cardioversion. Amiodarone Blocks Na+ channels 5–7 mg/kg IV up to Safest agent for use Bradycardia, QT prolongation, Can be used in the (affinity for inactivated 1500 mg per 24 h. in patients with hyperthyroidism, lung toxicity, Wolff–Parkinson– channels). Noncompetitive 400–800 mg PO daily, structural heart disease, argyria (blue discoloration White syndrome. ß- and ß-receptor for 3–4 wk, followed good efficacy in of skin) with chronic use inhibitor. by 100–400 mg PO maintaining NSR daily chronically

Sotalol Nonselective ß1- and 80–240 mg PO every Similar efficacy to Fatigue, depression, ß-blocking properties, but

ß2-blocking agent, 12 h quinidine, but fewer bradycardia, torsades de some positive inotropic prolongs action adverse effects. Better pointes, CHF activity. Lethal arrhythmias potential duration rate control because of possible. Adjust dose in ß-blocking properties. patients with renal insufficiency. Initiate on telemetry. Dofetilide Blocks rapid component 500 µg twice daily More effective than QT prolongation, torsades Must be strictly dosed of the delayed rectifier quinidine in conversion de pointes (2%–4% risk). according to renal

potassium current (IKγ), to and maintenance of function, body size, prolonging refractoriness NSR. and age. Contra- without slowing conduction indicated in patients with creatinine clearance <20 mL/min. Initiate on telemetry. Dronedarone Similar to amiodarone— 400 mg twice daily Well-tolerated and safe Gastrointestinal intolerance blocks sodium, potassium, and calcium channels

AF = atrial fibrillation; AV = atrioventricular; CHF = congestive heart failure; CNS = central nervous system; IV = intraventricular; LV = left ventricular; NPO = nil per os; NSR = normal sinus rhythm; PO = orally; VF = ventricular fibrillation; VT = ventricular tachycardia.

efficacy, so susceptibility to side ef- heart disease because they have been fects should guide the choice among associated with increased mortality 22. The Cardiac Arrhyth- mia Suppression Tri- them (Table 1). Drugs that block in these patients (22). Their side ef- al (CAST) Investiga- cardiac sodium channels (class I effects are due to unwanted sodium- tors. Preliminary report: effect of en- fect), such as flecainide and channel blockade in other organ sys- cainide and fle- propafenone, are useful in patients tems, such as the gastrointestinal cainide on mortality in a randomized trial without coronary heart disease or tract (resulting in anorexia or of arrhythmia suppression after my- advanced left ventricular dysfunc- esophageal reflux) and the central ocardial infarction. N tion. They should not be used in pa- nervous system. Other class I drugs, Engl J Med. 1989;321:406-12. tients with significant structural such as quinidine and procainamide, [PMID: 2473403]

7 December 2010 Annals of Internal Medicine In the Clinic ITC6-9 © 2010 American College of Physicians are used infrequently because of sotalol, or propafenone and found that af- noncardiac side effects and a concern ter mean follow-up of 16 months, recur- for proarrhythmia. Drugs that block rence of AF was 35% for amiodarone ther- potassium channels and thus have apy compared with 63% for sotalol or class III effects, such as sotalol and propafenone therapy (26). dofetilide, can prolong the QT inter- 23. Zimetbaum P. Amio- Some nonantiarrhythmic drugs, such darone for atrial fib- val and cause torsades de pointes. rillation. N Engl J as angiotensin-converting enzyme Med 2007;356;935- 941. Amiodarone can be used in patients inhibitors and statins, reduce the in- [PMID: 17329700] cidence of AF in patients with heart 24. Hohnloser SH, Crijns with advanced structural heart dis- HJ, van Eickels M, et failure, presumably because of their al; ATHENA Investi- ease. However, amiodarone can cause gators. Effect of permanent liver and lung toxicity antifibrotic effects (27). dronedarone on car- that is dose- and duration-dependent diovascular events in When is anticoagulation indicated atrial fibrillation. N (23). Hepatic toxicity is characterized Engl J Med. for patients with atrial 2009;361:1139-51. by hepatitis that can progress to cir- fibrillation? Epub 2009 Aug 30. rhosis. Pulmonary toxicity can devel- PMID: 19213680 Patients with paroxysmal, persist- 25. Lafuente-Lafuente C, op within 6 weeks or after years of Mouly S, Longas- ent, and permanent AF have the Tejero MA, Bergman therapy and most often manifests as JF. Antiarrhythmics same indications for anticoagula- for maintaining sinus cough and dyspnea. Pulmonary im- rhythm after car- aging can demonstrate a broad range tion. Anticoagulation is indicated dioversion of atrial when the risk for thromboem- fibrillation. Cochrane of findings, including segmental or Database Syst Rev diffuse infiltrates. Other side effects bolism exceeds that for anticoagu- 2007;(4):CD005049. 26. Roy D, Talajic M, Do- include thyroid dysfunction (hypo- lation-associated bleeding (8, 17). rian P, et al. Amio- For example, a patient older than darone to prevent thyroidism, hyperthyroidism), sun recurrence of atrial sensitivity, and ocular symptoms. 65 years with AF and no other risk fibrillation. Canadian Trial of Atrial Fibrilla- factors has a risk for thromboem- tion Investigators. N Dronedarone is a multichannel bolism of about 1%, which approxi- Engl J Med. 2000;342:913-20. blocking drug similar in structure mates the risk for major bleeding [PMID: 10738049] to amiodarone but without iodine. 27. CHARM Investiga- on warfarin when the international tors. Prevention of A study of 4300 patients demon- normalized ratio (INR) is between atrial fibrillation in patients with symp- strated its safety in patients with 2.0 and 3.0 (28-30). tomatic chronic AF who did not have advanced heart failure by candesartan in the Can- heart failure (24). As a result, Because of the delicate balance be- desartan in Heart tween risk and benefit, investigators failure: Assessment dronedarone is approved by the of Reduction in Mor- U.S. Food and Drug Administra- have developed guides to indicate tality and morbidity (CHARM) program. tion (FDA) to reduce hospitaliza- which patients with AF warrant Am Heart J. anticoagulation therapy. The most 2006;152:86-92. tions in patients with AF but is [PMID: 16838426] contraindicated for decompensated popular of these guides is the 28. Stroke Prevention in Atrial Fibrillation In- congestive heart failure. It is less ef- CHADS2 (Cardiac Failure, Hyper- vestigators. Lessons ficacious but better tolerated than tension, Age, Diabetes, and Stroke from the Stroke Pre- vention in Atrial Fib- amiodarone (24). [Doubled]) score (31, 32), which is rillation trials. Ann Intern Med. discussed in Table 2, and Table 3 2003;138:831-8. When should clinicians use presents recommendations for ther- [PMID: 12755555] antiarrhythmic drugs to prevent 29. Jung F, DiMarco JP. apy based on this score. Clinicians Treatment strategies the recurrence of atrial should consider long-term anti for atrial fibrillation. fibrillation? Am J Med. coagulation in patients who are at 1998;104:272-86. Antiarrhythmic drugs have only [PMID: 9552091] high risk for recurrent AF or have 30. Zabalgoitia M, modest effects compared with asymptomatic AF, intracardiac Halperin JL, Pearce placebo in prolonging the time to LA, et al. Trans- thrombus, or known risk factors for esophageal echocar- recurrence of AF (25) (Table 1). diographic corre- thromboembolism, which include lates of clinical risk Therefore, antiarrhythmic drug age ≥75 years, recent heart failure, of thromboem- therapy is generally considered bolism in nonvalvu- left ventricular dysfunction, dia- lar atrial fibrillation. effective if it reduces the frequency Stroke Prevention in betes mellitus, hypertension, and Atrial Fibrillation III of episodes and symptoms. Investigators. J Am previous thromboembolism. Many Coll Cardiol. The Canadian Trial of Atrial Fibrillation ran- clinicians use a cutoff of 65 rather 1998;31:1622-6. [PMID: 9626843] domly assigned 403 patients to amiodarone, than 75 years to initiate warfarin

© 2010 American College of Physicians ITC6-10 In the Clinic Annals of Internal Medicine 7 December 2010 therapy when the patient also has Table 2. Stroke Risk in Patients with Nonvalvular Atrial Fibrillation Not Treated coronary artery disease. with Anticoagulation According to CHADS2 Index* CHADS Risk Criteria Score A 2007 meta-analysis of 28 044 patients 2 with AF in 29 clinical trials reported that, Past stroke or TIA 2 compared with control patients, patients Age >75 y 1 on adjusted-dose warfarin (6 trials, 2900 Hypertension 1 Diabetes mellitus 1 participants) had 64% (95% CI, 49% to Heart failure 1 74%) fewer strokes and patients on an- tiplatelet agents (8 trials, 4876 partici- † Patients (n= 1733) Adjusted Stroke Rate (%/y) (95% CI) CHADS2 Score pants) had 22% (CI, 6% to 35%) fewer 120 1.9 (1.2 to 2.0) 0 strokes. Warfarin was superior to an- 463 2.8 (2.0 to 3.8) 1 tiplatelet therapy (relative risk reduction, 523 4.0 (3.1 to 5.1) 2 39% [CI, 22% to 52%]) (12 trials, 12 963 par- 337 5.9 (4.6 to 7.3) 3 ticipants), and both therapies were associ- 220 8.5 (6.3 to 11.1) 4 65 12.5 (8.2 to 17.5) 5 ated with a beneficial tradeoff between 5 18.2 (10.5 to 27.4) 6 strokes and major extracranial hemor- rhages (33). CHADS2 = Cardiac Failure, Hypertension, Age, Diabetes, and Stroke (Doubled); TIA = transient ischemic attack. * Reproduced from reference 5 with permission from the American Heart Association. Some recent data indicate that cur- † The adjusted stroke rate was derived from multivariate analysis assuming no aspirin use. rent incidences of stroke and bleed- Data from from references 30 and 31. ing are lower because of improved therapy for hypertension (34), and other recent data indicate that the Table 3. Antithrombotic Therapy for Patients with Atrial Fibrillation* incidence of major bleeding remains Risk Category Recommended Therapy high in the elderly (35). As a result, No risk factors Aspirin, 81–325 mg daily some experts advise alternative ther- 1 moderate risk factor Aspirin, 81–325 mg daily or apy for anticoagulation (36), but warfarin (INR, 2.0–3.0, target 2.5) consensus commendations for anti- Any high risk factor or Warfarin (INR, 2.0–3.0, target coagulation in patients with AF have more than 1 moderate 2.5)* risk factor not changed. Also, although genetic tests can identify variants in some of the enzymes that control warfarin Less-Validated or Weaker Moderate Risk Factors High Risk Factors metabolism (37), most experts do Risk Factors not recommend using these genetic Female sex Age ≥75 y Previous stroke, TIA, or embolism tests until clinical trials determine Age 65–74 y Hypertension Mitral stenosis † whether the information they pro- Coronary artery disease Heart failure Prosthetic heart valve ≥ vide can improve patient outcomes Thyrotoxicosis LV ejection fraction 35% from better warfarin dosing. Diabetes mellitus INR = international normalized ratio; LV = left ventricular; TIA = transient ischemic attack. What anticoagulation regimens * Reproduced from reference 5 with permission from the American Heart Association. should clinicians use in patients † If mechanical valve, target INR >2.5. with atrial fibrillation? Warfarin is the first choice for anticoagulation in patients with AF, and 31. Gage BF, Waterman the dose should be adjusted to an AD, Shannon W, et al. Validation of clini- INR of 2.0 to 3.0. Most patients cal classification schemes for predict- with prosthetic valves should have alone (39), but this combination is ing stroke: results the warfarin dose adjusted to an from the National not as effective as warfarin and has a Registry of Atrial Fib- INR of 2.5 to 3.5. Aspirin 325 mg/d bleeding risk equivalent to that of rillation. JAMA. 2001;285:2864-70. can be used as an alternative to war- warfarin (40). [PMID: 11401607] farin in the following circumstances: 32. van Walraven C, Hart RG, Wells GA, et al. A contraindication/allergy to warfarin; In patients at lower risk for throm- clinical prediction no previous stroke or transient is- boembolism, the clinician can start rule to identify patients with atrial fib- chemic attack; ≤75 years of age; and warfarin without a loading dose or rillation and a low risk for stroke while no hypertension, diabetes, or heart concurrent heparin, but patients at taking aspirin. Arch failure (38). Aspirin plus clopidogrel higher risk for thromboembolism Intern Med. 2003;163:936-43. prevents more strokes than aspirin should be hospitalized and given [PMID: 12719203]

7 December 2010 Annals of Internal Medicine In the Clinic ITC6-11 © 2010 American College of Physicians unfractionated heparin while waiting When should clinicians consider to achieve target levels for oral anti- nondrug therapies for patients coagulation. Data on use of low-mo- with atrial fibrillation? lecular-weight heparin in this setting Clinicians should consider nondrug are limited. therapy only after failure of drug therapy. Nondrug therapies include Warfarin should be used to achieve use of a catheter or surgery to ab- an INR of 2.0 to 3.0 for at least 3 late the atrioventricular node fol- to 4 consecutive weeks before car- lowed by permanent pacing, dioversion and at least 4 weeks af- catheter or surgical ablation of 33. Hart RG, Pearce LA, ter cardioversion in patients with Aguilar MI. Meta- parts of the atrium where AF be- analysis: antithrom- AF of undetermined duration or botic therapy to pre- gins, and occluding the left atrial vent stroke in AF lasting more than 48 hours. An appendage for stroke prevention. patients who have alternative approach is to perform nonvalvular atrial fibrillation. Ann Intern a transesophageal echocardiogram, Atrioventricular nodal catheter ab- Med. 2007;146:857- 67. [PMID: 17577005] and if clot is not present, anticoag- lation is used when pharmacologic 34. Hart RG, Tonarelli SB, ulate with heparin for 48 hours be- rate control cannot be achieved, Pearce LA. Avoiding central nervous sys- fore cardioversion followed by 4 usually because of intolerance to tem bleeding during weeks of warfarin anticoagulation antithrombotic ther- medications. This situation is most apy: recent data and (40). Patients with thrombus in the common in elderly patients or pa- ideas. Stroke. 2005;36:1588-93. left atrial appendage must be anti- tients with advanced heart failure [PMID: 15947271] coagulated for 4 weeks before car- 35. Hylek EM, Evans- or obstructive pulmonary disease, Molina C, Shea C, et dioversion regardless of the dura- which limits the use of β-blockers. al. Major hemor- rhage and tolerabili- tion of AF, and most clinicians Atrioventricular nodal ablation is ty of warfarin in the repeat the transesophageal first year of therapy highly effective (42) but requires among elderly pa- echocardiogram before cardiover- pacemaker insertion and can lead tients with atrial fib- sion to confirm that the thrombus rillation. Circulation. to progressive left ventricular dys- 2007;115:2689-96. has resolved. function. Pacing therapy without [PMID: 17515465] 36. Singer DE, Chang Y, atrioventricular nodal ablation has Warfarin has a narrow therapeutic Fang MC, et al. The little effect on the burden of AF net clinical benefit window, and its metabolism is af- of warfarin anticoag- but may be helpful in patients with ulation in atrial fibril- fected by many drug and dietary lation. Ann Intern paroxysmal AF and symptomatic interactions, requiring frequent Med. 2009;151:297- bradycardia, which is often a side 305. INR monitoring and dosage ad- [PMID: 19721017] effect of drug therapy. 37. Lenzini P. Wadelius justments. These limitations have M. Kimmel S, et al. prompted a search for alternative Integration of genet- Ablation of parts of the atrium ic, clinical, and INR anticoagulants. data to refine war- where AF begins has been shown farin dosing. Clinical to be effective in preventing recur- Pharmacol Ther. One clinical trial of dabigatran, a direct 2010;87:572-8. thrombin inhibitor, compared 2 doses (110 rent symptomatic AF in highly se- [PMID: 20375999] 38. The SPAF III Writing mg and 150 mg twice daily) of dabigatran lected patients (43). The ideal pa- Committee for the with warfarin in patients who had nonvalvu- tient is a young, otherwise healthy Stroke Prevention in Atrial Fibrillation In- lar AF. The lower dose of dabigatran was as ef- person without structural heart dis- vestigators. Patients fective as warfarin in preventing strokes, and with nonvalvular ease who has paroxysmal AF. Re- atrial fibrillation at it was associated with fewer bleeding compli- cent guideline statements have ac- low risk of stroke cations than warfarin. The higher dose of knowledged that it may be during treatment dabigatran was more effective than warfarin with aspirin: Stroke reasonable to provide this therapy Prevention in Atrial in preventing strokes and caused an equiva- Fibrillation III Study. for highly symptomatic patients JAMA. lent number of bleeding events (41). 1998;279:1273-7. with paroxysmal AF in whom an [PMID: 9565007] attempt at antiarrhythmic drug 39. ACTIVE Investigators. The FDA has approved dabigatran Connolly SJ. Pogue J. at 150 mg twice daily for preven- therapy has failed. This relatively Hart RG. Hohnloser SH. Pfeffer M. tion of stroke and systemic em- aggressive approach may prevent Chrolavicius S. Yusuf bolism in persons with AF and progressive AF-related morbidity S. Effect of clopidogrel added to aspirin creatinine clearance greater than 30 (e.g., residual risk for stroke, med- in patients with atrial fibrillation. N Engl mL/min. However, the FDA ap- ication side effects), but long-term J Med. proval does not allow a superiority benefit on mortality has not been 2009;360:2066-78. [PMID: 19336502] claim over warfarin. demonstrated. The effect of

© 2010 American College of Physicians ITC6-12 In the Clinic Annals of Internal Medicine 7 December 2010 ablation on mortality rates, quality appropriate for patients with AF, most of life, and health care costs will clinicians agree that patients should probably be better established dur- have regular follow-up to determine ing the coming years (44). Mini- the effectiveness of therapy. For many mally invasive surgical ablation is patients, monitoring warfarin antico- also available at specialized centers. agulation drives the frequency of follow-up. During these visits clinicians Occlusion of the left atrial ap- should also ask about palpitations, pendage to prevent strokes may easy fatigability, and dyspnea on exer- be an acceptable option in selected tion to determine whether symptoms high-risk patients who are not can- are adequately controlled. In addition, didates for oral anticoagulation they should measure resting and exer- therapy. Additional studies are cise heart rates to determine the ade- needed to verify the safety and ef- quacy of therapy. Patients who have fectiveness of these devices before not improved on rhythm-control drugs should be switched to rate-con- they can be recommended (45). 40. ACTIVE Writing trol drugs. Except for amiodarone, Group of the ACTIVE How should clinicians monitor Investigators. Clopi- which requires liver and thyroid func- dogrel plus aspirin patients with atrial fibrillation? tion studies every 6 months and chest versus oral anticoagulation for atrial fib- Although there are few studies radiography every year, routine tests rillation in the Atrial about what type of monitoring is for drug side effects are not necessary. fibrillation Clopido- grel Trial with Irbe- sartan for prevention of Vascular Events (ACTIVE W): a ran- Treatment... Atrial fibrillation treatment goals include reducing the frequency and domised controlled severity of symptoms, preventing stroke, and preventing tachycardia-related car- trial. Lancet. 2006;367:1903-12. diomyopathy. Selection of patients for anticoagulation with aspirin or warfarin [PMID: 16765759] 41. Connolly SJ, should be based on the CHADS2 score. Focus treatment first on rate control by us- Ezekowitz MD, Yusuf ing beta-blockers or calcium-channel antagonists aiming for a resting rate be- S, et al; RE-LY Steer- tween 60 and 110 beats per minute. Rhythm control may be reasonable in pa- ing Committee and Investigators. Dabi- tients who do not respond to rate control. Atrial ablation and atrioventricular gatran versus war- nodal ablation therapy may be appropriate for selected patients with highly farin in patients with symptomatic AF despite drug therapy. atrial fibrillation. N Engl J Med. 2009;361:1139-51. Epub 2009 Aug 30. CLINICAL BOTTOM LINE [PMID: 19717844] 42. Wood MA, Brown- Mahoney C, Kay GN, Ellenbogen KA. Clini- cal outcomes after ablation and pacing What’s New in This Update? recommend using these genetic therapy for atrial fib- In the Clinic rillation : a meta- last considered the tests until clinical trials determine analysis. Circulation. management of AF in 2008 (46). whether the information they pro- 2000;101:1138-44. [PMID: 10715260] Since then, several important vide improves patient outcomes. 43. Packer DL, Asir- vatham S, Munger changes have occurred. In the Dabigatran is a new anticoagulant TM. Progress in non- rate-control strategy for the drug that in early trials appears to be as pharmacologic therapy of atrial fibrilla- treatment of AF, the upper target effective as warfarin for prevent- tion. J Cardiovasc Electrophysiol. for heart rate at rest has increased ing thromboembolism but has 2003;14:S296-309. from 80 to 110 beats per minute fewer adverse effects (41). The [PMID: 15005218] 44. Crandall MA. Bradley (18). Dronedrone, a new antiar- FDA has recently approved it for DJ. Packer DL. Asir- rhythmic drug similar to amio- prevention of stroke and systemic vatham SJ. Contem- porary management darone in effectiveness but with embolism in patients with AF. of atrial fibrillation: update on anticoag- fewer side effects, has become Catheter ablation of parts of the ulation and invasive available for the management of atrium where AF begins has be- management strategies. Mayo Clinic patients with AF, primarily in the come more widely accepted for Proc. 2009;84:643-62. rhythm-control strategy (19, 24). preventing recurrent AF in select- [PMID: 19567719] 45. Cruz-Gonzalez I. Yan Although genetic tests can identi- ed patients, especially for young BP. Lam YY. Left atrial appendage exclu- fy variants in some of the en- and otherwise healthy persons sion: state-of-the-art. zymes that control warfarin me- without structural heart disease Catheter Cardiovasc Interv. 2010;75:806- tabolism (37), most experts do not who have paroxysmal AF (43, 44). 13. [PMID: 20088009]

7 December 2010 Annals of Internal Medicine In the Clinic ITC6-13 © 2010 American College of Physicians 46. Callans DJ. Atrial fibrillation. Ann Intern Practice Med. 2008;149:ITC4-1- 15. [PMID: 18981484] Improvement Do U.S. stakeholders consider What do professional 47. Snow V, Weiss KB, LeFevre M, et al. management of patients with atrial organizations recommend with Management of fibrillation when evaluating the regard to the management of newly detected atrial fibrillation: a clini- quality of care physicians deliver? patients with AF? cal practice guideline from the The Centers for Medicare & Medi- In 2003, the American College of American Academy caid Services has issued specifica- Physicians and the American of Family Physicians and the American tions for 74 measures that make up Academy of Family Physicians re- College of Physi- cians. Ann Intern the 2008 Physician Quality Report- leased a guideline on AF manage- Med. 2003;139:1009- ing Initiative, although none of them ment (47). The material presented 17. [PMID: 14678921] 48. Camm AJ, Kirchhof directly measure the quality of AF in this review has been updated and P, Lip GYH, et al. therapy. However, one of the stroke is consistent with the 2006 guide- Guidelines for the management of atri- measures examines the percentage of lines from the American Heart As- al fibrillation. The Task Force for the patients 18 years of age or older with sociation and American College of Management of Atri- a diagnosis of ischemic stroke or Cardiology (17) and the 2010 al Fibrillation of the European Society of transient ischemic attack and docu- guidelines by the European Society Cardiology (ESC). Eur Heart J (2010) doi: mented paroxysmal, persistent, or of Cardiology (48). 10.1093/eurheartj/e permanent AF who were prescribed hq278. First pub- lished online: August an anticoagulant at discharge. 29, 2010.

PIER Modules In the Clinic www.pier.acponline.org Access the PIER module on atrial fibrillation for updated, evidence- based information designed for rapid access at the point of care. Tool Kit Quality Measures c pier.acponline.org/qualitym/prv.html Access the PIER Quality Measure Tool, which links newly developed quality measures issued by the Ambulatory Quality Alliance and the Atrial Physician Quality Improvement QA Alliance and CMS’s Physician Quality Reporting Initiative program to administrative criteria for Fibrillation each measure and provides clinical guidance to help implement the measures and improve quality of care.

Patient Information lini www.annals.intheclinic/tools Download copies of the Patient Information sheet that appears on the following page for duplication and distribution to your patients. Anticoagulation Flow Sheet www.acponline.org/running_practice/quality_improvement/projects/cfpi/doc _anticoag.pdf Download a copy of a flow sheet to help manage patients on warfarin. Guidelines

www.americanheart.org/downloadable/heart/222_ja20017993p_1.pdf eC Access the American Heart Association, American College of Cardiology, and European Society of Cardiology joint 2006 guidelines for the management of patients with atrial fibrillation. www.annals.org/cgi/reprint/139/12/1009.pdf Access the American College of Physicians/American Academy of Family Physicians 2003 guidelines for the management of newly detected atrial fibrillation. www.nice.org.uk/Guidance/CG36 Access guidelines for the management of atrial fibrillation from the United Kingdom’s National Institute for Health and Clinical Excellence. http://eurheartj.oxfordjournals.org/content/early/2010/08/28/eurheartj.ehq27 8.full?sid=692900ce-f77f-4a46-9ef7-b2c317bc9413 Access 2010 guidelines for the management of atrial fibrillation from the Task Force for the Management of Atrial Fibrillation of the

European Society of Cardiology. In th

What is atrial fibrillation? • Atrial fibrillation is an irregular and sometimes very fast heart beat. Atrial fibrillation can come and go or be constant. It is more common in people with heart conditions and in older people than in younger people .

Atrial fibrillation can lead to 3 bad health outcomes: • Symptoms can make a person unable to do their usual activities.

• Over the long term, a very fast heartbeat can damage heart muscle.

• Atrial fibrillation can cause stroke when blood clots form in the heart and travel to the brain.

How would I know if I have atrial fibrillation? • Many people with atrial fibrillation have no symptoms and don’t know that they have it.

• When people have symptoms, they include palpitations (pounding in the chest), shortness of breath, or tiredness. What is the treatment? • Many patients with atrial fibrillation need to be on • Your doctor may see atrial fibrillation on an drugs to prevent stroke. Some people need only electrocardiogram (ECG) if an episode occurs during aspirin. Others need to take the blood thinner the test. warfarin.

• If you have symptoms that could be atrial fibrillation • Treatment usually includes drugs to slow the heart but your ECG is normal, your doctor may send you down or make it more regular. for a test that records your heartbeat while you go about your usual activities. • Less often, more aggressive treatment with catheters, surgery, or a pacemaker is needed. • If you have atrial fibrillation, your doctor may do an echocardiogram to look for heart problems. • Atrial fibrillation treatment can have dangerous side Echocardiograms use sound waves to take pictures effects. It is important to follow instructions and see of the heart. your doctor regularly.

For More Information

www.nlm.nih.gov/medlineplus/tutorials/atrialfibrillation/htm/_no_50_no _0.htm MedlinePlus

www.hrspatients.org/patients/heart_disorders/atrial_fibrillation/default.asp Heart Rhythm Society

circ.ahajournals.org/cgi/content/full/117/20/e340 American Heart Association Patient Information Patient CME Questions

1. An 88-year-old man is evaluated for treatment with metoprolol, episodes occur Which of the following is the most follow-up of persistent atrial fibrillation 3 to 4 times daily and last from a few appropriate adjustment to her with a rapid ventricular response minutes to several hours. During events, treatment? diagnosed several months ago. His initial he feels drained and unable to A. Add candesartan diagnosis was made during evaluation concentrate, with a sensation of an B. Add digoxin before cataract surgery. He underwent irregular heartbeat. He experiences C. Change hydrochlorothiazide to transesophageal echocardiography–guided dyspnea on exertion and lightheadedness, furosemide cardioversion after diagnosis, but the atrial but denies chest discomfort and syncope. D. Increase metoprolol dosage fibrillation recurred within 2 weeks. He Episodes are triggered by activity, caffeine, has been managed with warfarin, digoxin, and alcohol (both of which he 4. A 77-year-old woman is admitted to the and verapamil. He was initially prescribed discontinued upon diagnosis). He takes no hospital for intermittent dizziness over atenolol, but discontinued it because of medications other than the metoprolol. the past few days. She does not have side effects of fatigue and impaired On physical examination, blood pressure chest discomfort, dyspnea, palpitations, concentration and memory. He is entirely is 130/60 mm Hg and pulse is 70/min syncope, orthopnea, or edema. She asymptomatic despite an inadequately and regular. S1 and S2 are normal, and underwent coronary artery bypass graft controlled ventricular rate. He also has there is no murmur or extra heart surgery 6 years ago after myocardial hypertension treated with valsartan. He sounds. Estimated central venous infarction. She has hypertension, states that he generally is averse to taking pressure is 5 cm H2O, and the lungs are hyperlipidemia, and paroxysmal atrial more medications. clear. There is no edema. The remainder fibrillation with a history of rapid On physical examination, his blood of the physical examination is normal. ventricular response. Over the past pressure is 140/80 mm Hg, and his pulse is Which of the following is the most several years, she has “slowed down” and 147/min. Cardiac auscultation reveals an appropriate management for this patient? has had problems with memory, which irregularly irregular rhythm and a grade she attributes to aging. Medications are 2/6 holosystolic murmur. Estimated central A. Add amiodorone metoprolol, hydrochlorothiazide, B. Add digoxin venous pressure is 6 cm H2O. The lungs are pravastatin, lisinopril, aspirin, and clear to auscultation and there is no C. 24-hour ambulatory monitoring warfarin. D. Implanted loop recorder edema. Serum thyroid-stimulating On physical examination, her blood hormone level is normal. 3. A 60-year-old woman is evaluated for pressure is 137/88 mm Hg and her pulse A 24-hour ambulatory monitor follow-up after hospitalization 2 weeks is 52/min. Estimated central venous demonstrates a mean heart rate of pressure is 7 cm H O. The point of ago for pulmonary edema and volume 2 137/min, with a minimum rate of 70/min overload that readily resolved with maximum impulse is felt in the fifth and a maximum rate of 170/min. intravenous diuretics. She is currently intercostal space and at the midcostal Which of the following is the most feeling well without edema or shortness line. Cardiac auscultation reveals bradycardia with regular S and S , as appropriate management for this patient? of breath. A stress echocardiogram done 1 2 well as an S . A grade 2/6 early systolic in the hospital was negative for ischemia 4 A. Amiodarone murmur is heard at the left upper sternal B. Atrioventricular node ablation by and showed an ejection fraction of 60% and no significant valvular abnormalities. border. The lungs are clear to catheter and pacemaker placement She has a history of hypertension, auscultation. Edema is not present. C. Maze surgical procedure to ablate hyperlipidemia, and chronic atrial On telemetry, she has sinus bradycardia atrial fibrillation origin in the atrium fibrillation. She takes metoprolol (75 with rates between 40/min and 50/min, D. Radiofrequency ablation of atrial mg twice daily), hydrochlorothiazide, with two symptomatic sinus pauses of 3 fibrillation origin in the atrium warfarin, aspirin, and pravastatin. to 5 seconds each. 2. A 42-year-old man is evaluated for On physical examination, she is afebrile. Which of the following is the most recurrent, highly symptomatic paroxysmal Blood pressure is 150/90 mm Hg and pulse appropriate management for this patient? atrial fibrillation. He was initially is 50/min. Jugular veins are not distended, A. Add amiodarone and the lungs are clear. Cardiac diagnosed 6 months ago. His evaluation B. Discontinue metoprolol examination shows an irregularly irregular revealed no underlying cause and his C. Echocardiography resting electrocardiogram and rhythm with variable intensity of the S 1 D. Pacemaker implantation echocardiogram were normal. Despite with no murmurs. There is no edema.

Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP, accessed at http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/ to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.